Neem (Azadirachta Indica) is a plant which is used in India and Africa for the treatment of the symptoms of malarial fevers and a variety of other illnesses, including skin diseases and inflammations. Usually, a crude, unpurified aqueous or alcoholic extract of the Neem leaves, bark and/or roots is utilized for this symptomatic treatment. Neem seeds and oils are also used topically to treat skin infections and as insecticides and insect repellents.
The extraction of some antitumor substances from Neem bark has been reported by Pettit et al., Journal of Natural Products, Vol. 46 pp. 379-390 (1983) and Fujiwara et al., Carbohydrate Research 141, 168 (1985). These extracts were described as being useful for their toxic effects on cancer cells. However, these substances, like many other compositions used to treat cancer, are also toxic to noncancerous cells.
Similarly, several United States patents have reported Neem bark extracts which purportedly demonstrate antimitotic activity in fertilized sea urchin eggs and growth-inhibitory action against mouse sarcoma 180 ascites and solid tumors, and mouse L-5178Y cells. These patents are U.S. Pat. Nos. 4,515,785, 4,536,496 and 4,537,774 to Shimira et al.
The Neem tree (Azadirachta Indica) is a medicinal plant that grows wild in many parts of the world where the climate is warm, particularly in Asia and Africa. In Nigeria it is popularly called dogonyaro. All over Africa and Asia different parts of the Neem tree, leaves, bark and seed are employed as remedies for various human ailments. Neem medicinal products are widely used for treatment of skin diseases, inflammations, rheumatic diseases and fever. They are also employed extensively as antiparasitic agents in the treatment of helminthic and protozoal infections. In India, Neem oil and its isolates nimbidiol, nimbidin and diethylsulfides are used as anti-mycobacterial and antibacterial agents. In support of the diverse medicinal applications of Neem, extracts and isolated compounds from Neem exhibit various pharmacological activities. For instance, as an anti-inflammatory agent, an aqueous extract of Neem stem bark decreases both classical and alternative complement pathway activity, reducing complement- dependent responses, anaphylaxis, chemotaxis, opsonization and stimulation of macrophages and polymorphonucleoleucocytes. It also inhibits phorbol myristate acetate-stimulated chemiluminescence. Neem leaf extracts and isolated tetranortriterpenoids, gedunin and nimbolide, have been shown by various studies to inhibit the development of the human malarial parasite Plasmodium falciparum in vitro. Neem compounds, 7-acetyl neotrichilenone and 1,2-diapoxyazadiradione, were reported to inhibit the murine P-388 lymphocytic leukemia cell line with ED.sub.50 of 10 mg and 8.5 mg, respectively. Studies with various isolated Neem compounds have indicated that most of the medicinal and biological activity of the Neem is associated with the structural classes of limonoids, flavonoids, and macrolides, with sulfurated compounds playing minor roles.
Despite the extensive and centuries of use of Neem medicines, reports of toxicity in humans remain scanty. Experiments in mice suggest that various Neem compounds particularly oils, in large doses may produce toxicity. On the other hand, experiments in rats and dogs with nimbidin (a Neem compound) failed to demonstrate any systemic toxicity. Human subjects given Neem oil, 7 grams per person, orally, or 1 gram by intramuscular injection experienced no local or systemic side effects. Thus there is the expectation of low toxicity in its use as a drug and in handling the material. Interestingly, compounds isolated from the Neem leaves are azadiractin and related compounds which are very potent insect feeding repellents. This is a mechanism for the successful survival of this tree.